European Review for Medical and Pharmacological Sciences
Comparison of impact on seizure frequency
and epileptiform discharges of children with
epilepsy from topiramate and phenobarbital
Y.-Y. WANG, M.-G. WANG, D. YAO, X.-X. HUANG, T. ZHANG, X.-Q. DENG
Department of Neurology, Xuzhou Children's Hospital, Xuzhou, Jiangsu, P.R. China
Abstract. OBJECTIVE: To study the impact
on seizure frequency and epileptiform dis-
charges of children with epilepsy from topira-
mate (TPM) and phenobarbital (PB).
PATIENTS AND METHODS: Two hundred
cases children with epilepsy from August 2010
to August 2013 in our hospital were sampled
and randomly divided into two groups. The ob-
servation group was treated with TPM while the
control group with PB, and then comparing
seizure frequency, efficiency, and adverse re-
actions of two groups.
RESULTS: The reduced number of partial
seizures, generalized seizures, and total seizures
in the observation group were significantly high-
er than those in the control group, and the rate of
cure, markedly effective and total efficiency in
observation group were significantly higher than
those in the control group. However, the adverse
reactions in observation group were significantly
lower than those in the control group. Thus, dif-
ferences were statistically significant (p<0.05).
CONCLUSIONS: Compared with PB, TPM
showed a better effect on epilepsy treatment
with less adverse reactions which were worthy
of clinical recommendation.
Key Words:
Topiramate, Phenobarbital, Epilepsy, Seizure fre-
quency, Epileptiform discharges.
Introduction
Epilepsy is commonly known as Yanger
Feng, it is one of the most common chronic dis-
eases of the nervous system in children, the preva-
lence rate is from 3 to 61,2. Epilepsy is brought
about by the abnormal synchronous discharge of
brain cells because of a variety of causes, and it
can lead to the sudden onset of brain dysfunction.
Its clinical manifestation is diversified; it may lead
to many patients performances such as conscious-
Corresponding Author: Xingqiang Deng, MD; e-mail: dengxingqiang1962@163.com
2016; 20: 993-997
ness change or loss, body twitch, sensory abnor-
malities, and special behavior, etc.3,4. In the past,
people had less knowledge and studies on epilepsy
which led to that many patients were not scientifi-
cally treated and their seizure control was running
below expectations. Since the 1980s, a large num-
ber of new drugs have come out and have greatly
improved the treatment efficiency of epilepsy and
it is not incurable disease anymore5. Since Au-
gust 2010, topiramate (TPM) has showed its sig-
nificant effect on epilepsy treatment in our hospital
and the efficiency report is as follows.
Patients and Methods
Patients
Two hundred cases children with epilepsy from
August 2010 to August 2013 in our hospital were
observed and randomly divided into two groups. The
criteria used for the diagnosis: 1. Repeated attack,
which can be self-relieved. 2. With acute onset. Re-
stored after the treatment. 3. No sign of symptoms
shown before the onset but existing inducement. 4.
Abnormal EEG. The observation group included 55
male and 45 female patients (aged from 4.1 2.5),
among them, 67 patients had generalized seizures
and 33 patients had partial seizures. The control
group included 56 male and 44 female patients (aged
from 4.3 1.9), among them, 67 patients had gener-
alized seizures and 33 patients had partial seizures.
The difference in gender, age and condition of pa-
tients between the two groups was not statistically
significant (p>0.05); thus, it is comparable.
Treatment Methods
To give a medicine based on the weight of
children. The observation group was given TPM
treatment, and its initial oral intake was 0.5 to 1
mg/(kgd) and 2 times/day, then added 0.5 to 1
993
 Y.-Y. Wang, M.-G. Wang, D. Yao, X.-X. Huang, T. Zhang, X.-Q. Deng
mg/(kgd) every week until intake turned to 4 to 8
mg/ (kgd) after 4 to 8 weeks and maintained it.
The control group was given phenobarbital (PB)
treatment, and its initial oral intake was 2 to 3
mg/(kgd) and 1-2 times/day, then added up to 3
to 5 mg/(kgd) by the second week. There was
more than 3 months follow-up to patients in two
groups after reaching maintained medicine intake.
Observation Index
Observation index is the observation and com-
parison of seizure frequency, treatment efficien-
cy, and adverse reactions of patients in two
groups before and after three months treatment.
Treatment Efficiency Evaluation
According to patients condition after treatment,
it could be cure-EEG showed that epileptiform dis-
charges disappeared, be markedly-EEG showed
that epileptiform discharge was significantly re-
duced, be effective-EEG showed that epileptiform
discharge reduced, and be invalid-EEG showed
that epileptiform discharge had no change or in-
creased6. Among them, the rate of markedly effec-
tive was equal to the sum rate of cure and marked-
ly, while total efficiency was equal to the sum rate
of cure, markedly and effective.
Statistical Analysis
With statistical software SPSS 13.0 (IBM,
New York, US), analysis of data comparison was
worked out by 2test while measurement data
with t-test, and if p< 0.05, the difference was sta-
tistically significant.
Results
The Comparison of the Seizure Numbers
of the Two Groups
The reduced number of partial seizures was
(6.31.3) times, generalized seizures was (7.12.5)
Table I. The comparison of seizure frequency with different treatment methods.
Group Reduce number of
partial seizures (n = 33)
Observation group 6.3 1.3*
Control group 4.1 1.5
t 6.367
p 0.000
Note: Compared with the control group, *p<0.05.
994
times, and total seizures were (6.72.2) times in
observation group which were significantly higher
than those (reduced number of partial seizures was
(4.11.5) times, generalized seizures were
(6.11.8) times, and total seizures were (5.91.7))
in control group. Thus, differences were statistical-
ly significant (p<0.05), which meant that treatment
efficiency in observation group is better than that
in the control group. See below Table I.
The Comparison of the Treatment
Efficiency with the Different Treatment
Methods
The rate of cure, markedly effective, and total
efficiency in observation group were 42%
(42/100), 80.00% (80/100), and 88.00% (88/100),
which were significantly higher than those
[28.00% (28/100), 55.00% (55/100), 77.00%
(77/100)] in control group. Thus, the difference
was statistically significant (p<0.05), which meant
that the treatment efficiency in the observation
group is better than that in the control group. See
below Table II.
Adverse Reactions
There were no seizure numbers increased, ill-
ness deteriorated, routine blood, liver and kidney
became abnormal, and electrocardiography
(ECG) and electroencephalogram (EEG)
changed in any children patients during the treat-
ment period. All 200 patients in this research
were treated for three months. Among those in
the observation group, there were somnolence in
15 patients, anorexia in 2 patients, fatigue in 2
patients, cool response in 1 patient, and weight
loss in 2 patients, and all of those adverse reac-
tions were alleviated through adding dose slowly
and taking medicine after meals during addition-
al medicine dose period. Meanwhile, there were
mild aminotransferase rise in 4 patients, somno-
lence in 34 patients, headache in 3 patients, ner-
vous hyperactivity in 2 patients. Differences be-
Reduce number of Reduce number of
generalized seizures (n = 67) total seizures (n = 100)
7.1 2.5* 6.7 2.2*
6.1 1.8 5.9 1.7
2.657 2.877
0.009 0.004
 TQ and -TP may protect the sciatic nerve and femoral muscle
Table II. Comparison of the clinical efficiency between two groups with different treatment methods.
Group n Cure Markedly
Observation group 100 42 (42.00)* 38 (38.00)
group
Control group 100 28 (28.00) 27 (27.00)
x2 4.308 2.758
p 0.038 0.097
Note: Compared with the control group, *p<0.05.
tween the two groups were statistically signifi-
cant (p<0.05), which meant that the adverse reac-
tions in the observation group was significantly
less than those in the control group.
Discussion
In 1980, TPM was synthesized initially. In
1986, it was used for epilepsy treatment for the
first time. In 1995, it joined in the market in the
UK firstly. In 1999, it joined in China market.
Compared with the traditional antiepileptic drug
(AED), TPM has many advantages such as mul-
tiple action mechanisms that play a stronger and
broad-spectrum role in epilepsy treatment [7,8].
There were three unique action mechanisms of
TPM: 1) TPM blocked Na+ channels to inhibit
repeated and sustained discharge. 2) GABA-A
receptor increased the activity of GABA so as to
enhance neural inhibition of GABA mediacy. 3)
TPM intercepted AMPA subtype of glutamate
receptors to block nerve excitability of mediacy9.
The results of this study showed that the re-
duced number of partial seizures, generalized
seizures and total seizures in the observation
group were significantly higher than those in
control group, which accorded with the report of
Siniscalchi et al10 and others. The reason of this
may be that the structure of TPM is different
from other types of AED, and TPM is monosac-
charide derivatives with sulfanilamide group and
has multiple anti-epilepsy mechanisms. TPM can
block Na+ channels to inhibit repeated and sus-
tained discharge, enhance neural inhibition of
GABA mediacy by increasing the activity of
GABA, and block nerve excitability of AMPA
subtype of glutamate mediacy11. TPM is an effi-
cient, broad-spectrum and safe AED, it is not on-
Markedly Total
Effective Invalid effective rate efficiency
8 (8.00)* 12 (12.00)* 80 (80.00)* 88 (88.00)*
22 (22.00) 23 (23.00) 55 (55.00) 77 (77.00)
7.686 4.190 14.245 4.190
0.006 0.041 0.000 0.041
ly suitable for the partial seizures but the gener-
alized seizures, and it also can be absorbed com-
pletely and quickly through oral intake.
Tran et al12 reported that antiepileptic charac-
teristic of TPM was different from propyl ben-
zene two nitrogen, and it may take effect through
regulating less sensitive GABA subtype receptor
of propyl benzene two nitrogen. TPM could
block the start of subtype Kainate/AMPA with
kainic acid while had no effect on subtype NM-
DA receptor. Moreover, TPM could also inhibit
the effect of part of carbonic anhydrase
isozyme13,14. Meanwhile, PB belonged to the bar-
biturate AED and it could enhance inhibitory
GABA effect on epileptiform discharge and dif-
fusion which had advantages such as fast and
good effect, thus it had priority of using as
epilepsy treatment medicine for a long time.
However, Marion et al15 thought that PB could
affect children IQ and cognitive function of chil-
dren and had sedation; thus, they suggested that
PB should be used less as far as possible.
The results of this study showed that the treat-
ment efficiency in the observation group was
significantly higher than that in the control
group, which accorded with the report of Dewis
et al16 and others17-20. Adverse reactions of TPM
mainly related to central nervous system (CNS)
and it were mostly in the light of moderate toler-
ance range21-25. Most adverse reactions of TPM
in this study were somnolence, anorexia, fatigue,
and weight loss, and most somnolence and
anorexia disappeared after taking medicine in 10
to 15 days, which suggested that adverse reac-
tions happened easily during additional medicine
dose period and most of them were tolerant and
transient26-29. The reason of weight loss was still
not clear and it may be related to anorexia. Be-
sides, the result showed that TPM did not lead to
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 Y.-Y. Wang, M.-G. Wang, D. Yao, X.-X. Huang, T. Zhang, X.-Q. Deng
common adverse reactions such as blood and
pancreatic injury and allergic reactions as other
AED. Moreover, it led to better tolerance of chil-
dren patients.
Conclusions
Compared with PB, TPM shows the better ef-
fect on epilepsy treatment with less adverse reac-
tions which is worthy of clinical recommendation.
- 13) UKAWSKI K, JANOWSKA A, JAKUBUS T, CZUCZWAR SJ. In-
Conflict of Interest
The Authors declare that they have no conflict of interests.
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